Effect of birth weight and 12 weeks of exercise training on exercise-induced AMPK signaling in human skeletal muscle

Abstract

Subjects with a low birth weight (LBW) display increased risk of developing type 2 diabetes (T2D). We hypothesized that this is associated with defects in muscle adaptations following acute and regular physical activity, evident by impairments in the exercise-induced activation of AMPK signaling. We investigated 21 LBW and 21 normal birth weight (NBW) subjects during 1 h of acute exercise performed at the same relative workload before and after 12 wk of exercise training. Multiple skeletal muscle biopsies were obtained before and after exercise. Protein levels and phosphorylation status were determined by Western blotting. AMPK activities were measured using activity assays. Protein levels of AMPKα1 and -γ1 were significantly increased, whereas AMPKγ3 levels decreased with training independently of group. The LBW group had higher exercise-induced AMPK Thr(172) phosphorylation before training and higher exercise-induced ACC2 Ser(221) phosphorylation both before and after training compared with NBW. Despite exercise being performed at the same relative intensity (65% of Vo2peak), the acute exercise response on AMPK Thr(172), ACC2 Ser(221), AMPKα2β2γ1, and AMPKα2β2γ3 activities, GS activity, and adenine nucleotides as well as hexokinase II mRNA levels were all reduced after exercise training. Increased exercise-induced muscle AMPK activation and ACC2 Ser(221) phosphorylation in LBW subjects may indicate a more sensitive AMPK system in this population. Long-term exercise training may reduce the need for AMPK to control energy turnover during exercise. Thus, the remaining γ3-associated AMPK activation by acute exercise after exercise training might be sufficient to maintain cellular energy balance.

Acute exercise increases insulin sensitivity in adult sheep: a new preclinical model

“…45). The similar muscle glycogen content measured in these animals in the unexercised state and 18 h after the exercise bout in ovine skeletal muscle in the present study is also consistent with a lack of training effect, since exercise training in sheep and in humans increases glycogen contents of resting skeletal muscle (33,36,40). It is possible, however, that the lack of change in glycogen content in skeletal muscle sampled 18 h after acute exercise in the present study might partially reflect incomplete restoration of glycogen depleted during exercise (54).…”

Exercise as an intervention to improve metabolic outcomes after intrauterine growth restriction

“…Surprisingly, although insulin sensitivity measured by homeostasis model assessment of insulin resistance (HOMA-IR) remained similar before and after intervention in AGA children, insulin resistance worsened during the lifestyle intervention in the obese SGA children despite weight loss occurring (109). In young adult men, although exercise training induced a normal increase in insulin action in SGA individuals, they seemed more susceptible to the negative effects of bed rest than AGA men (79,80).…”

“…At present, despite evidence of altered mitochondrial volume and function in animal models of IUGR, as discussed below, there is little evidence for this in humans, at least in young adults. AGA and SGA young adults have similar skeletal muscle mitochondrial function (14) and normal mitochondrial mRNA and protein expression of oxidative phosphorylation genes including the master regulator PGC-1␣ (80,93). Whether mitochondrial function or mitochondrial protein or mRNA expression is reduced after IUGR in older populations has not been investigated in humans to date.…”

“…There have been only three intervention studies of exercise and physical activity in SGA humans. Of these, one was a one-year lifestyle intervention (which included exercise) in obese children (109), while two shorter studies were conducted in young men, investigating metabolic responses to 12 weeks of exercise training or detraining responses after 9 days of bed rest (79,80). Surprisingly, although insulin sensitivity measured by homeostasis model assessment of insulin resistance (HOMA-IR) remained similar before and after intervention in AGA children, insulin resistance worsened during the lifestyle intervention in the obese SGA children despite weight loss occurring (109).…”

“…Few intervention studies have been performed in humans. In the two intervention studies reported to date, a one-year lifestyle intervention in obese 10-year-old children improved insulin resistance less in SGA than in AGA children (109), and a 12-week exercise training intervention in young adult men decreased body fat similarly in SGA and AGA groups, with similar effects of training on insulin sensitivity but with greater impairment of insulin action after bed rest in the SGA group (79,80). The beneficial effects of adult exercise after IUGR have also been demonstrated in rats, although there is some suggestion that the improvements may be less than in control rats (62).…”